Advances in the physiology, neurobiology, and molecular biology of thermoreception in animal models have outpaced research on human thermoreception. The present continuing project seeks to incorporate this new knowledge into psychophysical studies that test hypotheses about basic mechanisms of human temperature sensitivity. Previous research on the project uncovered evidence of an extensive overlap in sensitivity between the classically defined senses of warmth and cold and the sense of pain, and of interactions between touch and temperature that modify the qualitative and quantitative dimensions of temperature perception. The proposed research builds on these and other more recent findings to investigate how nonpainful temperatures are sensed via multisensory interactions among the cutaneous sensory systems. Specifically, Aim 1 will test a simple model of how low-threshold thermal afferent fibers may converge and interact with thermal and nociceptive neurons in the spinothalamic tract. Tests of the model, which is based in part on psychophysical evidence that afferent fibers with sensitivities in the range of warm fibers and cold fibers can relay stimulation to the pain pathway, will provide basic information about the mechanisms of nonpainful heat and the possible contribution of putative warm fibers and cold fibers to the thresholds for heat pain and cold pain. Aim 2 will test hypotheses about the involvement of recently discovered transient receptor potential (TRP) channels in nonpainful perception of cold and heat using topical application of chemical agents that have been shown to modulate these channels. Finally, Aim 3 will investigate the parameters of tactile stimulation that underlie the ability of simple contact to suppress thermal sensitivity, particularly nociceptive sensations perceived at innocuous temperatures. Of interest is whether this suppression arises from a general inhibitory action of touch on pain or from a specialized mechanism that attenuates sensitivity to contact thermal stimulation. By testing novel hypotheses about the relationship of temperature sensitivity to pain, the proposed research will yield new information about the full range of excitatory thermal inputs to the pain system as well as the full range of inhibitory controls which the thermal and tactile systems exert on the pain system. The project therefore has the potential to provide new insights into how disruption of normal interactions between the somesthetic and pain systems may play a role in the development of neuropathic pain in clinical disorders such as fibromyalgia, multiple sclerosis, and stroke. PUBLIC HEALTH RELEVANCE: The proposed research will provide new, basic information about the human sensitivity to temperature and its relationship to pain. Psychophysical methods will be used to investigate predictions made from a neural model of how peripheral neurons that sense nonpainful stimuli may interact with neurons in the central nervous system that serve the sense of pain. In particular, experiments will test hypotheses about whether peripheral neurons that respond to mild cooling, heating or touch may excite or inhibit nociceptive neurons in the spinothalamic tract. By testing new hypotheses about the relationship of temperature sensitivity to pain the proposed project has the potential to provide insights into the causes of painful neuropathies that can be triggered by mild temperatures, such as those associated with multiple sclerosis, fibromyalgia, and stroke.